The effectiveness of combinations of cytostatic chemotherapeutic drugs with radiation will be determined for several endpoints. Drugs to be used include adriamycin, actinomycin D, cyclophosphamide, BCNU, cis-platinum, and bleomycin. Tumor response will be evaluated by the delay of growth of 3 tumors, EMT6 sarcoma, RIF-1 sarcoma, and MDAH/MCa4 carcinoma, tested in syngeneic mice; and by clonogenic survival of tumor cells, determined in vitro, from RIF-1 and EMT6 tumors after treatment in vivo. Changes in the fractions of proliferating (P) and non-proliferating (Q) clonogenic tumor cells will be studied in EMT6 and RIF-1 tumors, using the microcolony 3HTdR labeling method. Combined modality effects will also be studied in the spinal cord, lung, kidney, and skin. Treatment regimens will be evaluated for effects on the spread of lymphatic or blood-borne metastases from footpad-implanted KHT tumors. Cells grown in vitro will be used to test for potentially valuable cytostatic agents other than the 6 drugs listed, and to investigate mechanisms of enhanced effectiveness in combined modality regimens. Intensive investigation of fractionated drug/radiation regimens, as well as baseline single dose experiments, will be undertaken. Testing in the tumor and normal tissue systems is intended ultimately to provide information about the therapeutic ratio of different combinations of modalities, i.e., the effect of treatment on malignant cells relative to the effects on normal tissues.